Eucaryotic cells rapidly produce a small set of proteins, originally known as heat shock proteins and now also as stress proteins, in response to a broad range of environmental stresses. Neither the function nor the physiologic role of stress proteins in stressed animals is known. The purposes of this proposal are to obtain clues to the function of the most abundant stress protein by purification and biochemical characterization and to evaluate possible links between stress proteins and febrile responses in animals including effects of stress hormones on cultured mammalian cells. The major mammalian stress proteins, starting with the kilodalton stress protein (sp71) and a related stress cognate protein (scp73) will be purified using heat-shocked rats as a source. Putative biological functions of stress proteins involving ATPase and autophosphorylation and stabilization of stress-labile proteins will be evaluated. A search will be undertaken for endogenous stressors in (i) sera and tissues from febrile dogs with cyclic neutropenia, (ii) incubated rodent bladder urothelium, and (iii) cultured mammalian cells responding to ACTH and glucocorticoids. Experiments are included to develop a recent novel finding in our laboratory that sp71 and its cognate scp73 are fatty acid-binding proteins. These studies will substantially expand our knowledge of cellular stress responses and their significance for the cellular basis of disease.